Variant 2-240891632-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001085437.3(MAB21L4):c.646G>A(p.Gly216Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,456,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

MAB21L4
NM_001085437.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.916

Variant links:

Genes affected

MAB21L4 (HGNC:26216): (mab-21 like 4)

MAB21L4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052646995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAB21L4	NM_001085437.3 linkuse as main transcript	c.646G>A	p.Gly216Arg	missense_variant	2/5	ENST00000388934.5	NP_001078906.3
MAB21L4	NM_001282921.2 linkuse as main transcript	c.199G>A	p.Gly67Arg	missense_variant	2/5		NP_001269850.2
MAB21L4	NM_024861.4 linkuse as main transcript	c.142G>A	p.Gly48Arg	missense_variant	2/5		NP_079137.4
MAB21L4	XM_011511877.2 linkuse as main transcript	c.646G>A	p.Gly216Arg	missense_variant	3/6		XP_011510179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAB21L4	ENST00000388934.5 linkuse as main transcript	c.646G>A	p.Gly216Arg	missense_variant	2/5	2	NM_001085437.3	ENSP00000373586	P1	Q08AI8-1
MAB21L4	ENST00000307486.12 linkuse as main transcript	c.199G>A	p.Gly67Arg	missense_variant	2/5	1		ENSP00000302779		Q08AI8-2
MAB21L4	ENST00000402775.6 linkuse as main transcript	c.142G>A	p.Gly48Arg	missense_variant	2/5	2		ENSP00000385338		Q08AI8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245152

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000892

AC:

AN:

1456996

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

725016

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000826

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.646G>A (p.G216R) alteration is located in exon 2 (coding exon 2) of the C2orf54 gene. This alteration results from a G to A substitution at nucleotide position 646, causing the glycine (G) at amino acid position 216 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.6

DANN

Benign

0.69

DEOGEN2

Benign

0.0020

.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.080

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0020

B;.;B

Vest4

0.10

MutPred

0.35

.;.;Gain of solvent accessibility (P = 0.0263);

MVP

0.067

MPC

0.093

ClinPred

0.034

GERP RS

-3.2

Varity_R

0.079

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over